ClinVar Miner

Submissions for variant NM_031885.5(BBS2):c.1895G>A (p.Arg632His)

dbSNP: rs138043021
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV001121738 SCV001280384 uncertain significance Bardet-Biedl syndrome 2 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Fulgent Genetics, Fulgent Genetics RCV002480494 SCV002788365 uncertain significance Bardet-Biedl syndrome 2; Retinitis pigmentosa 74 2022-05-07 criteria provided, single submitter clinical testing
Invitae RCV002558204 SCV003522710 uncertain significance Bardet-Biedl syndrome 2022-05-14 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 632 of the BBS2 protein (p.Arg632His). This variant is present in population databases (rs138043021, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with BBS2-related conditions. ClinVar contains an entry for this variant (Variation ID: 888430). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant disrupts the p.Arg632 amino acid residue in BBS2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 21052717, 22401627, 25541840, 28559085). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Preventiongenetics, part of Exact Sciences RCV003413925 SCV004109218 uncertain significance BBS2-related condition 2023-03-16 criteria provided, single submitter clinical testing The BBS2 c.1895G>A variant is predicted to result in the amino acid substitution p.Arg632His. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.013% of alleles in individuals of South Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/16-56530894-C-T). An alternate variant at the same amino acid position has been document as pathogenic for autosomal recessive BBS2-related disorders (p.Arg632Pro, alt nomenclature p.Arg634Pro; Katsanis et al. 2001. PubMed ID: 11567139; Bin et al. 2009. PubMed ID: 11567139; Consugar et al. 2015. PubMed ID: 25412400; Shevach et al. 2015. PubMed ID: 25541840). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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